Department of Biomedical Engineering

Indian Institute of Technology Hyderabad (IITH) is a premier institute of science and technology established in 2008. IITH has been consistently ranked in the&nbsp;<a href="https://iith.ac.in/reports/" rel="noopener noreferrer">top 10 institutes</a>&nbsp;in India for Engineering&nbsp;<a href="https://www.nirfindia.org/2021/EngineeringRanking.html" rel="noopener noreferrer" target="_blank">according to NIRF</a>&nbsp;making it one of the most coveted schools for science and technology in the country.

IITH offers&nbsp;<a href="https://iith.ac.in/academics/under-graduate/">undergraduate programs</a>&nbsp;in all the classical engineering disciplines, applied sciences, design, as well as several modern interdisciplinary areas. Students are given a flexibility to explore a broad set of areas, and potentially pursue a minor or double major in a discipline that is not their own. Students who wish to seek a deeper understanding of their own discipline are strongly encouraged to get involved in cutting-edge research with the help of a faculty to mentor them, and earn an Honors in their own field.

The very foundation of IIT Hyderabad is based on&nbsp;<a href="https://iith.ac.in/research/">research and innovation</a>. The vibrant research culture is evident from the number of patents and publications that IITH produces consistently every year. IITH offers&nbsp;<a href="https://iith.ac.in/academics/programmes-offered/">graduate programs</a>&nbsp;at both a masters, and a doctoral level, in several diverse areas. There are separate programs for technology, design, science, and liberal arts. The&nbsp;<a href="https://iith.ac.in/academics/post-graduate/">MTech program</a>&nbsp;is offered in various modes and durations to cater to the ever-growing need of postgraduate level professionals in the country.

IITH encourages and supports&nbsp;<a href="https://iic-iith.netlify.app/index.html" rel="noopener noreferrer" target="_blank">innovation and entrepreneurship</a>&nbsp;at every stage. The minor program in entrepreneurship is open to all students of IITH, and many of the courses are offered by industrialists who are entrepreneurs themselves. There are various&nbsp;<a href="https://iith.ac.in/research/centres-incubators/">innovation centers and incubators</a>&nbsp;that promote entrepreneurship and help mentor young innovators. IITH has been very successful in building tie-ups with leading academic institutions around the globe.

IITH enjoys a very special relationship with Japanese universities and industries that goes beyond academic and research collaborations. In fact, some of the iconic buildings in IITH campus will carry the signature of Japanese architecture.

IITH creates a unique holistic ecosystem for education that offers interactive learning, a very flexible academic structure, cutting-edge research, strong industry collaboration, and entrepreneurship. This is an environment which enables students and faculty to translate their dreams into realities.

IIT Hyderabad

The study of variation in biomechanical properties is a significant diagnostic tool for examining malignancy in tissues. Elastography is a potential technique that is used for qualitative and quantitative assessment of abnormal tissues. Optical coherence elastography is a highly efficient and promising technique for inspecting soft biological tissues with microscale resolution. In the present work, we report the elastographic measurement of tissue-mimicking phantoms of varying stiffness using reflection mode holographic imaging. The sinusoidal surface excitation is produced by an electromechanical actuator on the sample over a set of frequencies and the phase map of the surface wave is reconstructed using a phase-shifting algorithm. The preliminary results are well correlated with previously reported literature. The current work has high potential applications for quantifying the biomechanical properties of in-vivo and ex-vivo tissues in clinical practice. © 2023 SPIE.

World University root node

Progress in Biomedical Optics and Imaging - Proceedings of SPIE

Elastographic measurements on tissue phantoms by imaging Rayleigh wave propagation

As hypoxia plays a significant role in the formation and maintenance of cartilage tissue, aiming to develop native hypoxia-mimicking tissue engineering scaffolds is an efficient method to treat articular cartilage (AC) defects. Cobalt (Co) is documented for its hypoxic-inducing effects in vitro by stabilizing the hypoxia-inducible factor-1α (HIF-1α), a chief regulator of stem cell fate. Considering this, we developed a novel three-dimensional (3D) bioprintable hypoxia-mimicking nano bioink wherein cobalt nanowires (Co NWs) were incorporated into the poly(ethylene glycol) diacrylate (PEGDA) hydrogel system as a hypoxia-inducing agent and encapsulated with umbilical cord-derived mesenchymal stem cells (UMSCs). In the current study, we investigated the impact of Co NWs on the chondrogenic differentiation of UMSCs in the PEGDA hydrogel system. Herein, the hypoxia-mimicking nano bioink (PEGDA+Co NW) was rheologically optimized to bioprint geometrically stable cartilaginous constructs. The bioprinted 3D constructs were evaluated for their physicochemical characterization, swelling-degradation behavior, mechanical properties, cell proliferation, and the expression of chondrogenic markers by histological, immunofluorescence, and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) methods. The results disclosed that, compared to the control (PEGDA) group, the hypoxia-mimicking nano bioink (PEGDA+Co NW) group outperformed in print fidelity and mechanical properties. Furthermore, live/dead staining, double-stranded DNA (dsDNA) content, and glycosaminoglycans (GAGs) content demonstrated that adding low amounts of Co NWs (&lt;20 ppm) into PEGDA hydrogel system supported UMSC adhesion, proliferation, and differentiation. Histological and immunofluorescence staining of the PEGDA+Co NW bioprinted structures revealed the production of type 2 collagen (COL2) and sulfated GAGs, rendering it a feasible option for cartilage repair. It was further corroborated by a significant upregulation of the hypoxia-mediated chondrogenic and downregulation of the hypertrophic/osteogenic marker expression. In conclusion, the hypoxia-mimicking hydrogel system, including PEGDA and Co2+ ions, synergistically directs the UMSCs toward the chondrocyte lineage without using expensive growth factors and provides an alternative strategy for translational applications in the cartilage tissue engineering field. © 2023 American Chemical Society.

Department of Materials Science and Metallurgical Engineering

ACS Applied Materials and Interfaces

3D Bioprintable Hypoxia-Mimicking PEG-Based Nano Bioink for Cartilage Tissue Engineering

The clinical challenge in the successful management of oral cancer malignancy remains in the inaccuracy of detecting regional invasion potential and inefficient treatment of recurrent tumors. The presence and extent of bone invasion by the oral tumor are of critical importance as they can influence the preoperative strategy altering the prognosis outcome. Here, we are examining the patient-specific osteotropism of oral carcinoma using a bone derived extracellular matrix. The extracellular matrix (ECM) was obtained from caprine bone by a combination of demineralization, delipidation and decellularization (D3) techniques. The bone D3-derived ECM (BdECM) tissue was characterized for analyzing the effective removal of cells, minerals, and lipids with an intact structure and chemical composition. The human adipose-derived stem cells (ADSCs) on the osteomatrix (BdECM derived hydrogel) exhibited excellent cell viability and early osteogenic differentiation capacity in vitro. Furthermore, the osteomatrix polarized monocytes towards an anti-inflammatory phenotype (M2 macrophage) indicating its low immunogenicity. In the second phase of this study, we isolated and established primary cancer cell cultures from patient-derived tissue exhibiting the cancer stem cell marker phenotype (EpCAM+/CD44high/CD24−). Moreover, the presence of side population (SP) cells confirmed a contributing factor for resistance to cancer therapy. The spheroid formed from primary cells embedded in the osteomatrix was used as a test-bed to monitor the invasion profile and screening of anti-cancer drugs. Our 3D test platform captured the inter-patient heterogeneity by displaying variation in the degree of invasion and response towards tested doses of anticancer drugs. Altogether, our data emphasize the necessity of a tissue-specific in vitro preclinical model for the evaluation of oral carcinogenesis and drug sensitivity. © 2023 The Royal Society of Chemistry.

Biomaterials Science

Osteomatrix as a personalized 3D tissue-specific invasion test-bed for oral carcinoma

The synthesis of carbon dots using plant leaves is a facile and economically viable approach. Here we report the development of lipid-coated red fluorescent carbon dots (LRCDs), a biocompatible and stable nanomaterial, utilizing Clitoria ternatea leaves. The red fluorescent carbon dots (RCDs) were prepared by hydrothermal method, followed by lipid coating using rotary evaporation for imaging-guided phototherapy. RCDs generate heat in tandem with NIR laser irradiation and could therefore be employed as a photothermal agent in cancer therapy. Additionally, the fluorescent nature of RCDs can be utilized in bioimaging. The fabricated RCDs displayed a characteristic fluorescent emission maximum at 672 nm with a shoulder peak at 723 nm. Hydrophobicity is a major drawback associated with the RCDs, which limits their therapeutic efficiency due to poor biodistribution and rapid clearance. To address this limitation, we coated RCDs with soya lecithin to generate hydrophilic LRCDs with better bioavailability and therapeutic effectiveness. Further analysis using MTT assay reveals high biocompatibility and a distinct photothermal ablation potency of LRCDs against L929 and 4T1 cells, respectively. LRCDs could potentially be synthesized on a large scale and used for a variety of applications due to their low-cost, and biocompatibility. © 2023

Photodiagnosis and Photodynamic Therapy

Lipid-coated red fluorescent carbon dots for imaging and synergistic phototherapy in breast cancer

Maintenance of homeostasis is the primary function of the immune system. It detects the threats posed by pathogens, cancer, and tissue damage and mounts an immune response. The immunological memory dispensed by the immune system prevents or minimizes a second attack by the pathogen. Owing to the advent of new technologies, the comprehension of the immune system has widened, thus opening new horizons to modulate the immune system against any threat. Modulating the immune system with several biological and synthetic molecules mainly targets the innate and adaptive immune system to mount responses against several types of cancers, pathogenic infections, and autoimmune diseases. Polymers are widely used in several biological applications. The various characteristics of polymers, including molecular weight and tunable properties to modulate certain biological functions, have rendered them an ideal candidate for developing state-of-the-art therapeutic interventions. Extensive studies by various researchers across the globe have unraveled the potential of several synthetic and natural polymers to exhibit immunostimulatory activities. These polymers act as pattern recognition receptors (PRR) agonists to activate and engage the immune system. Despite polymeric nanoformulations and scaffolds being used to ferry molecular cargo, targeted delivery to specific cells, and interact with biological molecules, the innate potential of the polymers to influence the immune system is still little understood. From this perspective, this review discusses the very commonly used natural polysaccharides, which are also polymers, and their innate immunomodulatory potentials, mostly focusing on the molecular pathways influenced by the polysaccharides in the immunomodulation process. Further, the challenges associated with the application of polysaccharides and the potential solutions have also been discussed. © 2023 Elsevier Ltd

Department of Chemistry

European Polymer Journal

Immunomodulatory natural polysaccharides: An overview of the mechanisms involved

With the advent of nucleosome/nucleotide intercalating drugs, DNA-based nanocarriers have recently gained impetus. However, most of the newly proposed DNA nanosystems are rather complex, thereby having low scalability and translatability. In this study, we propose a simple DNA nanomatrix core encapsulated within a chitosan shell, which is expected to enhance the encapsulation efficiency of intercalating drugs. This has been demonstrated using proflavine hemisulfate (PfHS), a model intercalating agent that shows improved ROS generation, among other anticancerous properties. The release of the drug from the nanomatrix is triggered by providing a heat trigger using IR-792 perchlorate, a known NIR photothermal sensitizer. © 2023 American Chemical Society.

Department of Biotechnology

ACS Macro Letters

High-Affinity DNA Nanomatrix: A Platform Technology for Synergistic Drug Delivery and Photothermal Therapy

Bioprinted tissues are currently being utilized for drug and cosmetic screening mostly, but the long-term goal is to achieve human scale functional tissues and organs for transplantation. Hence, recapitulating the multiscale architecture, 3D structures, and complexity of native tissues is the key to produce bioengineered tissues/organs. Decellularized extracellular matrix (dECM)-based biomaterials are widely being used as bioinks for 3D bioprinting for tissue engineering applications. Their potential to provide excellent biocompatibility for the cells drove researchers to use them extensively. However, the decellularization process involves many detergents and enzymes which may contribute to their loss of mechanical properties. Moreover, thermal gelation of dECM-based hydrogels is typically slow which affects the shape fidelity, printability, and physical properties while printing complex structures with 3D printing. But, thermally gelled dECM hydrogels provide excellent cell viability and functionality. To overcome this, a novel dual crosslinking of unmodified dECM has been proposed in this study to render shape fidelity and enhance cell viability and functionality. The dECM-based bioink can be initially polymerized superficially on exposure to light to achieve immediate stability and can attain further stability upon thermal gelation. This dual crosslinking mechanism can maintain the microenvironment of the structure, hence allowing the printing of stable flexible structures. Optimized concentrations of novel photo crosslinkers have been determined and printing of a few complex-shaped anatomical structures has been demonstrated. This approach of fabricating complex scaffolds employing dual crosslinking can be used for the bioprinting of different complex tissue structures with tissue-specific dECM based bioinks. © 2023 Elsevier B.V.

Biomaterials Advances

3D bioprinting of tissue constructs employing dual crosslinking of decellularized extracellular matrix hydrogel

Organic π-systems with strong absorption in the near-infrared (NIR) region are promising candidates for photothermal therapy (PTT) and photodynamic therapy (PDT). However, the synthesis of NIR π-systems involves several steps and many of them display poor photothermal conversion efficiency (PTCE). Here we present the synthesis of a tetraimide-based donor-acceptor NIR π-system, 2EHex-B having absorbance in the range of 350–900 nm. Importantly, 2EHex-B is synthesized in two steps with a 70 % high yield. Moreover, 2EHex-B shows excellent PTCE up to 50 % and good biocompatibility when encapsulated in liposomes. The liposome coated 2EHex-B, (L-2EHex-B) showed good thermal stability and efficiently kills cancer cells via PTT. Additionally, L-2EHex-B shows good reactive singlet oxygen generation ability when irradiated with a 750 nm laser. 3D cell culture model - multicellular spheroids test was performed to evaluate the efficiency of PTT. The spheroids treated with L-2EHex-B after NIR light irradiation showed increased cell death from the core of the tumor toward the periphery. The easy access to 2EHex-B makes it a potential candidate for minimally invasive cancer treatment. © 2023 Wiley-VCH GmbH.

ChemBioChem

An Easily Accessible NIR-Absorbing Tetraimide Dye and its Biotherapeutics Based Photothermal and Photodynamic Therapy

Magnetic nanoparticle (MNP) delivery systems are promising for targeted drug delivery, imaging, and chemo-hyperthermia of cancer; however, their uses remain limited primarily due to their toxicity associated with reactive oxygen species (ROS) generation, targeted delivery, and biodegradation. Attempts employing polymer coatings to minimize the toxicity, along with other challenges, have had limited success. We designed a novel yet generic ‘one-for-all’ polypropylene sulphide (PPS) coated magnetic nano-delivery system (80 ± 15 nm) as a multi-faceted approach for significant biocompatibility improvement, loading of multiple drugs, ROS-responsive delivery, and combined chemo-hyperthermia therapy for biomedical applications. Three distinct MNP systems (15 ± 1 nm) were fabricated, coated with PPS polymer, and investigated to validate our hypothesis and design. Simultaneous degradation of MNPs and PPS coatings with ROS-scavenging characteristics boosted the biocompatibility of MNPs 2-3 times towards non-cancerous fibroblasts (NIH3T3) and human epithelial cells (HEK293). In an alternating magnetic field, PPS-MNPs (MnFe) had the strongest heating characteristics (SAR value of 240 W g−1). PPS-MNP drug-loaded NPs were efficiently internalised into cells and released 80% of the drugs under tumor microenvironment-mimicking (pH 5-7, ROS) conditions, and demonstrated effective chemo-hyperthermia (45 °C) application for breast cancer cells with 95% cell death in combined treatment vs. 55% and 30% cell death in only hyperthermia and chemotherapy respectively. © 2023 The Royal Society of Chemistry.

Nanoscale

Polypropylene sulphide coating on magnetic nanoparticles as a novel platform for excellent biocompatible, stimuli-responsive smart magnetic nanocarriers for cancer therapeutics

In this study, we evaluated the performance of tonic and phasic components of Electrodermal activity (EDA) using machine learning algorithms for accurately recognizing emotions. The EDA signals considered for this study were obtained from Continuously Annotated Signals of Emotion (CASE) dataset. Initially, we pre-processed and decomposed the EDA into tonic and phasic components using cvxEDA method. Further, we extracted the temporal and morphological features from both tonic and phasic. Finally, we tested the performance of various combinations of features using machine learning algorithms such as logistic regression, support vector machine (SVM), and random forest. Our results revealed that the tonic contributes significant information for emotional state classification. Further, the temporal features of the phasic were able to discriminate most of the emotions (p<0.05). In particular, the scary emotion was well discriminated against other emotions. Results of classification revealed that SVM performed best in classifying emotional states. The results of our process pipeline, which incorporated tonic, temporal features, and SVM, showed impressive classification performance with average accuracy, sensitivity, specificity, precision, and f1-score of 78.96%, 57.92%, 85.97%, 62.32%, and 56.48%, respectively. Our findings indicate that our proposed models could potentially be used to detect the positive and negative emotions in healthcare settings. © 2023 World Scientific Publishing Company.